Synthesis and study of L-cysteine-arylamides as potential protease inhibitors

Vol. 1, 2019 - 108976
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Resumo

HIV-protease and renin are aspartyl proteases with many structural similarities. Since patients on highly active antiretroviral therapy (HAART) are at a high risk of developing some irreversible side effects, such as hypertension, this project aims the drug design for the development of potential inhibitors bearing dual activity towards these proteases. The synthesis of L-cysteine-derived arylamides using more sustainable methodologies were studied. The methodologies employing the coupling reagent CDI in neat conditions and/or using green solvents proved to be quite efficient and very clean, with yields between 80%-90%. Screening in vitro assays have been played with cysteine, serine and aspartyl proteases in order to verify the inhibitory action of these compounds. Results are promising, and some arylamides used at concentrations around 2.5 µM showed complete inhibition of these proteases, being smaller than those found in the literature.

Palavras-chave
drug design
Arylamides
Coupling reagents
HIV-protease
Renin